What are CGRP Monoclonal Antibodies?

CGRP monoclonal antibodies: Quick Look

UsePrevent migraine, typically used for people with chronic or severe migraines.
EffectivenessProven effectiveness in large, high-quality clinical trials.
Migraine-specific?Yes
Prescription?Yes
Side effectsAllergic reaction to the drug, injection site reaction
Taken how?Injection (Aimovig, Ajovy, Emgality)
Intravenous infusion (Vyepti)
Drugs in this class
Brand Name(s)Generic Name
Aimovigerenumab-aooe
Ajovyfremanezumab-vfrm
Emgalitygalcanezumab-gnlm
Vyeptieptinezumab-jjmr
Brand Name(s)Generic Name
Aimovigerenumab-aooe
Ajovyfremanezumab-vfrm
Emgalitygalcanezumab-gnlm
Vyeptieptinezumab-jjmr

CGRP (calcitonin gene-related peptide) monoclonal antibodies prevent migraine. The approval of the first CGRP antibodies in 2018 was a breakthrough in migraine treatment. They are the first migraine-specific preventive medications. There are currently four approved CGRP antibodies. CGRP antibodies do not stop a migraine attack once it has started.
 

Dysfunctional nerve signaling and migraine

Migraine is a result of dysfunctional nerve signaling. Key players are the trigeminal nerves and CGRP, a signaling molecule. The trigeminal nerve runs from the brain to the face. It is responsible for sensation in the face and head, and some jaw movement. CGRP is a small protein that transmits signals in the brain. Sensory nerves produce and release CGRP. Drugs that block CGRP are useful for preventing and treating migraine.

Other names for this class of drugs are: CGRP mAbs, CGRP inhibitors, or CGRP antagonists.

How do CGRP antibodies block CGRP?

CGRP antibodies disrupt the CGRP process. The lock-and-key analogy is helpful for understanding how they do this. The CGRP protein is the key. The CGRP receptor is the lock. When the key opens the lock, the pain process begins or worsens. Medications that block the lock or change the shape of the key interfere with the function of CGRP and are useful treatments for migraine.

One CGRP antibody blocks the “lock:”

Three other CGRP antibodies attach to the “key”:

How well do they work?

The CGRP antibodies have not been directly compared in clinical trials. It is always difficult to compare results from different studies. Studies may have different designs and populations. With that in mind, the results from large phase 2 and 3 trials are summarized below.

Treating episodic migraine

In general, CGRP antibodies prevent 3 or 4 migraine days per month for people with episodic migraine. This is an average, so your results may be better or worse. For comparison, the beta-blockers and anticonvulsants approved for migraine prevent about 1 to 2 migraine days per month. Specific results from clinical trials of the CGRP antibodies are:

  • 4.7 fewer migraine days per month with Emgality, 120 mg5
  • 3.9 fewer migraine days per month with Vyepti, 100 mg6
  • 3.7 fewer migraine days per month with 225 mg monthly Ajovy7
  • 3.2 fewer migraine days per month with Aimovig, 70 mg8

The trials also reported how many people with episodic migraine had at least 50 percent fewer migraine days per month. The results showed this outcome in:

  • 62 percent of people treated with Emgality5
  • 50 percent of people treated with Vyepti, 100 mg6
  • 48 percent of people treated with 225 mg monthly Ajovy7
  • 43 percent of people treated with Aimovig, 70 mg8

Treating chronic migraine

In general, CGRP antibodies prevent 4 to 7 migraine days per month for people with chronic migraine. This is an average, so your results may be better or worse. Specific results from clinical trials are:

  • 7.6 fewer migraine days per month with Vyepti, 100 mg9
  • 6.6 fewer migraine days per month with Aimovig, 70 mg10
  • 5 fewer migraine days per month with 225 mg monthly Ajovy11
  • 4.6 fewer headache days per month with Emgality12

The trials also reported how many people had at least 50 percent fewer migraine days per month. The results showed this outcome in:

  • 55 percent of people treated with Vyepti, 100 mg9
  • 40 percent of people treated with Aimovig, 70 mg10
  • 41 percent of people treated with 225 mg monthly Ajovy11
  • 28 percent of people treated with Emgality12

What are the possible side effects?

The side effects of CGRP antibodies are generally mild or moderate.9-12 Redness or pain at the injection site is common.1-4 A small number of patients in clinical trials had an allergic reaction to the medications. Aimovig was associated with constipation.1 Some patients treated with Vyepti in clinical trials had an upper respiratory infection (cold).4

These drugs were approved based on 3- to 6-month studies.5-12 To draw conclusions about long-term safety, more time and experience with CGRP antibodies is needed.13

The long-term data available so far are encouraging. The FDA collects real-world safety data about all approved drugs. In the first 6 months after the CGRP antibodies launched, the most commonly reported problems were headache, migraine, symptoms of migraine, and injection-site reactions.14One-year studies of Aimovig and Emgality have shown that the drugs continue to be safe and effective.15,16

These are not all the possible side effects of CGRPs. Patients should talk to their doctor about what to expect with CGRP treatment. You should begin no medication or supplement without first checking with your health care provider and should let them know of any other prescriptions, OTCs, and herbals you are taking to ensure there are no interactions.

What are the differences between Aimovig, Emgality, Ajovy, and Vyepti?

The four CGRP antibodies are taken on different schedules and in different ways. Aimovig and Emgality are given by injection once per month.1,3 Ajovy is given by injection every 1 or 3 months.2 Vyepti is given as a 30-minute infusion once every 3 months.4

The decision about which CGRP antibody to use may depend on insurance coverage. As described above, each of these medications work in a slightly different way. All of them are effective at preventing migraine. The side effects are minimal and similar.

How are CGRP monoclonal antibodies different from CGRP gepants?

There is a family of drugs called the CGRP gepants. This class includes Ubrelvy™ and Nurtec™. Because the drug families have similar names, the difference between CGRP antibodies and CGRP gepants can be confusing.

The monoclonal antibodies and gepants both target CGRP. However, these classes of medication have different uses. CGRP antibodies are taken to prevent migraine. Gepants are acute treatments for migraines at the start of an attack.17,18

What are the 4 letters at the end of the scientific name?

Many medications have two names. There is a brand name, such as Aimovig, Ajovy, Emgality, or Vyepti. There is a scientific name, such as erenumab-aooe, fremanezumab-vfrm, galcanezumab-gnlm, or eptinezumab-jjmr.

You may have wondered about the 4 letters at the end of the scientific name. A deeper dive into the science will explain their purpose. The CGRP monoclonal antibodies are biologic drugs. Biologic drugs are proteins made by the cells of living organisms. They are much more complex than conventional medications, which are made by chemical processes.

Unlike generic copies of a chemical drug, biosimilars are not exact copies of the original (“reference”) drug. Companies have to prove that there are no differences between a biosimilar and the original biologic that will impact patients.

A biosimilar is very much like the original biologic. But not exactly alike. The FDA wanted the names to reflect this. So biologics and their biosimilars share a scientific name, but each has its own 4-letters suffix.19

Currently, there are no biosimilar CGRP monoclonal antibodies. But someday there might be. The suffix will help patients, health care providers, and regulatory agencies keep track of which drug a person takes.

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Written by: Sarah O'Brien | Last Reviewed: July 2020